Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-02-22
2001-09-18
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S185000
Reexamination Certificate
active
06291446
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is broadly directed to a method for inhibiting activation of cytomegalovirus (CMV), especially reactivation of latent CMV. The present invention is particularly directed to the use of a particular class of isozyme selective Protein Kinase C (PKC) inhibitors for treating CMV infection and disease conditions associated with CMV infection, e.g., CMV mononucleosis and CMV syndromes in immunocompromised hosts.
2. Description of Related Art
CMV, which was initially isolated from patients with congenital cytomegalic inclusion disease, is now recognized as an important pathogen in all age groups. In addition to inducing severe birth defects, CMV causes a wide spectrum of disorders in older children and adults, ranging from an asymptomatic, subclinical infections to a mononucleosis syndrome in healthy individuals and to disseminated diseases in the immunocompromised. Human CMV is one of several related species-specific viruses that cause similar diseases in various animals. All are associated with the production of characteristic enlarged cells.
CMV has a worldwide distribution. Approximately 1 percent of newborns in the United States are infected with CMV, and the percentage is higher in many less-developed countries. Once infected, an individual probably carries the virus for life. Most commonly these infections remain latent. However, with a compromise of T-lymphocyte-mediated immunity, as occurs following organ transplantation or in association with lymphoid neoplasms and certain acquired immunodeficiencies, CMV reactivation syndromes develop frequently.
No specific and/or effective therapy is available for CMV infections. Treatment of ongoing CMV syndromes has been largely unsuccessful to date in transplant recipients and in patients with AIDS. Interferons, vidarabine, and acyclovir have failed, whether used alone or in combination. Newer nucleoside derivatives, such as 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), have shown considerable activity against CMV in vitro. DHPG also shows promise in early clinical trials against CMV retinitis, colitis, and pneumonitis.
As one can appreciate, the presently available treatments for CMV infection and syndromes are scarce and not yet completely effective. There remains a need in the art to develop more ways to treat CMV infection and syndromes.
SUMMARY OF INVENTION
It is an object of the invention to provide a method for inhibiting CMV activation.
It is another object of the invention to provide a method for inhibiting CMV major immediate early gene activity.
It is yet another object of the invention to provide a method for treating CMV infection.
It is still another object of the invention to provide a method for treating CMV induced syndromes.
These and other objects of the invention are provided by one or more of the embodiments provided below.
In one embodiment of the invention there is provided a method for inhibiting activation of CMV which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a particular class of protein kinase C inhibitors.
In another embodiment of the invention there is provided a method for inhibiting CMV major immediate early gene activity which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a particular class of protein kinase C inhibitors.
In yet another embodiment of the invention there is provided a method for treating CMV infection which comprises administering to a mammal in need of such treatment a therapeutically effective amount of the protein kinase C inhibitor.
In still another embodiment of the invention there is provided a method for treating CMV induced syndromes which comprises administering to a mammal in need of such treatment a therapeutically effective amount of the protein kinase C inhibitor.
The present invention identifies compounds which are effective in treating CMV infection and disease conditions associated therewith, e.g.,CMV mononucleosis and CMV syndromes in immunocompromised hosts.
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Slobbe-van Druneb et al, Virus Research, vol. 48(2), pp. 207-213, 1997.*
Wilkinson et al. “Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C” Biochem J. (1993) 294 pp. 335-337.
Marlea E.P Slobbe-Van Drunen et al. “Activation of proten kinase C enhances the infection of endothelial cells by human cytomegalovirus” Virus Research, vol. 48, No. 2, 1997 pp. 207-213.
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Darkes Paul R.
Eli Lilly and Company
Travers Russell
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